Treatment of relapsed or refractory FLT-3 acute myelogenous leukemia with a triplet regimen of hypomethylating agent, venetoclax, and gilteritinib

Leuk Lymphoma. 2024 Mar;65(3):372-377. doi: 10.1080/10428194.2023.2292473. Epub 2024 Jan 2.

Abstract

Relapsed or refractory (R/R) acute myeloid leukemia (AML) with FMS-like tyrosine kinase 3 (FLT3) mutations remains a difficult and hard to treat entity. Gilteritinib is a potent oral FLT-3 inhibitor that improves overall survival in R/R AML, but studies are limited in combining gilteritinib with a hypomethylating agent and venetoclax treatment backbone (HMA-VEN-GILT). Here we report our experience with HMA-VEN-GILT for 22 R/R FLT3 AML patients. HMA-VEN-GILT yielded an ORR of 77.3% (17/22), CR 4.5% (1/22), CRi 13.6% (3/22), MLFS 59.1% (13/22). Median follow-up was 10.4 months with a relapse rate of 29.4% (5/17), median time to relapse of 69 days (range 35-298 days), 6-month overall survival of 84%, and median OS of 10.1 months. Additionally, 36.4% (8/22) of patients proceeded to hematopoietic stem cell transplant. In conclusion, HMA-VEN-GILT for the treatment of R/R FLT3 AML is feasible and can be used as a bridge to allogeneic transplantation.

Keywords: FLT-3 AML; FLT-3 inhibitor; gilteritinib; refractory AML; relapsed AML.

MeSH terms

  • Aniline Compounds*
  • Bridged Bicyclo Compounds, Heterocyclic*
  • Humans
  • Leukemia, Myeloid, Acute* / diagnosis
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / genetics
  • Pyrazines*
  • Recurrence
  • Sulfonamides*
  • fms-Like Tyrosine Kinase 3* / genetics

Substances

  • gilteritinib
  • venetoclax
  • fms-Like Tyrosine Kinase 3
  • Aniline Compounds
  • Pyrazines
  • Sulfonamides
  • Bridged Bicyclo Compounds, Heterocyclic